Non-invasive device and method for the diagnosis of pulmonary vascular occlusions

ABSTRACT

The invention involves a device and method for ascertaining the functioning of the respiratory system and determining whether a pulmonary embolism is present. The device comprises an apparatus containing sensors for measuring the oxygen and carbon dioxide concentrations as well as the volume of air inhaled and exhaled by a patient. From this data, a processor computes the ratio of carbon dioxide to oxygen for the volume of expired air and displays the results on a screen. By comparing the results to predetermined normal values, an accurate determination can be made regarding the presence of a pulmonary embolism.

BACKGROUND OF THE INVENTION

[0001] 1. Field of Invention

[0002] The present invention relates generally to vascular occlusions ofthe respiratory system, and more particularly to non-invasive devicesand methods for the diagnosis of a pulmonary embolism and relateddisorders.

[0003] 2. Description of Prior Art

[0004] A pulmonary embolism occurs when an embolus become lodged in lungarteries, thus blocking blood flow to lung tissue. An embolus is usuallya blood clot, known as a thrombus, but may also comprise fat, amnioticfluid, bone marrow, tumor fragments, or even air bubbles that block ablood vessel. Unless treated promptly, a pulmonary embolism can befatal. In the United States alone, around 600,000 cases occur annually,10 percent of which result in death.

[0005] The detection of a pulmonary embolism is extremely difficultbecause signs and symptoms can easily be attributed to other conditionsand symptoms may vary depending on the severity of the occurrence.Frequently, a pulmonary embolism is confused with a heart attack,pneumonia, hyperventilation, congestive heart failure or a panic attack.In other cases, there may be no symptoms at all.

[0006] Often, a physician must first eliminate the possibility of otherlung diseases before determining that the symptoms, if any, are causedby a pulmonary embolism. Traditional diagnostic methods of testinginvolve blood tests, chest X-rays, and electrocardiograms. These methodsare typically more effective in ruling out other possible reasons thanfor actually diagnosing a pulmonary embolism. For example, a chest x-raymay reveal subtle changes in the blood vessel patterns after an embolismand signs of pulmonary infarction. However, chest x-rays often shownormal lungs even when an embolism is present, and even when the x-raysshow abnormalities they rarely confirm a pulmonary embolism. Similarly,an electrocardiogram may show abnormalities, but it is only useful inestablishing the possibility of a pulmonary embolism.

[0007] As a pulmonary embolism alters the ability of the lungs tooxygenate the blood and to remove carbon dioxide from the blood, onemethod of diagnosing the condition involves taking a specimen ofarterial blood and measuring the partial pressure of oxygen and carbondioxide in the arterial blood (i.e., an arterial blood gas analysis).Although a pulmonary embolism usually causes abnormalities in thesemeasurements, there is no individual finding or combination of findingsfrom the arterial blood gas analysis that allows either a reliable wayto exclude or specific way of diagnosing pulmonary embolism. Inparticular, at least 15-20% of patients with a documented pulmonaryembolism have normal oxygen and carbon dioxide contents of the arterialblood. Accordingly, the arterial blood analysis cannot reliably includeor exclude the diagnosis of a pulmonary embolism.

[0008] The blood D-dimer assay is another diagnostic method that hasbecome available for commercial use. The D-dimer protein fragment isformed when fibrin is cleaved by plasmin and therefore producednaturally whenever clots form in the body. As a result, the D-dimerassay is extremely sensitive for the presence of a pulmonary embolismbut is very nonspecific. In other words, if the D-dimer assay is normal,the clinician has a reasonably high degree of certainty that nopulmonary embolism is present. However, many studies have shown aD-dimer assay is only normal in less than ⅓ of patients and thusproduces a high degree of false positives. As a result, the D-dimerassay does not obviate formal pulmonary vascular imaging in mostpatients with symptoms of a pulmonary embolism.

[0009] In an attempt to increase the accuracy of diagnostic, physicianshave recently turned to methods which can produce an image of apotentially afflicted lung. One such method is a nuclear perfusion studywhich involves the injection of a small amount of radioactive particlesinto a vein. The radioactive particles then travel to the lungs wherethey highlight the perfusion of blood in the lung based upon whetherthey can penetrate a given area of the lung. While normal results canindicate that a patient lacks a pulmonary embolism, an abnormal scandoes not necessarily mean that a pulmonary embolism is present. Nuclearperfusion is often performed in conjunction with a lung ventilation scanto optimize results.

[0010] During a lung ventilation scan, the patient inhales a gaseousradioactive material. The radioactive material becomes distributedthroughout the lung's small air sacs, known as alveoli, and can beimaged. By comparing this scan to the blood supply depicted in theperfusion scan, a physician may be able to determine whether the personhas a pulmonary embolism based upon areas that show normal ventilationbut lack sufficient perfusion. Nevertheless, a perfusion scan does notalways provide clear evidence that a pulmonary embolism is the cause ofthe problem as it often yields indeterminate results in as many as 70%of patients.

[0011] Pulmonary angiograms are popular means of diagnosing a pulmonaryembolism, but the procedure poses some risks and is more uncomfortablethan other tests. During a pulmonary angiogram, a catheter is threadedinto the pulmonary artery so that iodine dye can be injected into thebloodstream. The dye flows into the regions of the lung and is imagedusing x-ray technology, which would indicate a pulmonary embolism as ablockage of flow in an artery. Pulmonary angiograms are more useful indiagnosing a pulmonary embolism than some of the other traditionalmethods, but often present health risks and can be expensive. Althoughfrequently recommended by experts, few physicians and patients arewilling to undergo such an invasive procedure.

[0012] Spiral volumetric computed tomography is another diagnostic toolthat has recently been proposed as a less invasive test which candeliver more accurate results. The procedure's reported sensitivity hasvaried widely, however, and it may only be useful for diagnosing anembolism in central pulmonary arteries as it is relatively insensitiveto clots in more remote regions of the lungs.

[0013] These pulmonary vascular imaging tests have several disadvantagesin common. Nearly all require ionizing radiation and invasiveness of, ata minimum, an intravenous catheter. The imaging tests also typicallyinvolve costs of more than $1,000 for the patient, take more than twohours to perform, and require special expertise such as a trainedtechnician to perform the tests and acquire the images and aboard-certified radiologist to interpret the images. Notably, none arecompletely safe for patients who are pregnant. As a result of theseshortcomings, the imaging procedures are not available in manyoutpatient clinic settings and in many portions of third worldcountries.

3. OBJECTS AND ADVANTAGES

[0014] It is a principal object and advantage of the present inventionto provide physicians with an instrument for non-invasively diagnosingpulmonary vascular occlusions.

[0015] It is an additional object and advantage of the present inventionto provide an instrument that accurately diagnoses pulmonary vascularocclusions.

[0016] It is a further object and advantage of the present invention toprovide an instrument for measuring and interpreting pulmonary testdata.

[0017] Other objects and advantages of the present invention will inpart be obvious, and in part appear hereinafter.

SUMMARY OF THE INVENTION

[0018] In accordance with the foregoing objects and advantages, thepresent invention provides a device and method for non-invasivelydiagnosing a pulmonary embolism. The device of the present inventioncomprises a breathing tube having sensors for measuring the flow of airinto and out of a patient's lungs while a data processing unitsimultaneously determines the oxygen and carbon dioxide concentrations.The device further includes a display screen for visually graphing theresulting calculations and providing a visual means for determining thelikelihood that a pulmonary embolism is present based upon a change inmeasured gas concentrations.

BRIEF DESCRIPTION OF THE DRAWINGS

[0019]FIG. 1 is an illustration of a respiratory system duringinhalation.

[0020]FIG. 2 is an illustration of a respiratory system duringexhalation.

[0021]FIG. 3 is an illustration of a respiratory system afflicted with apulmonary vascular occlusion during exhalation.

[0022]FIG. 4 is a schematic representation of the system of the presentinvention.

[0023]FIG. 5 is a perspective view of an attachment to the invention.

[0024]FIG. 6 is an illustration of a display screen readout.

DETAILED DESCRIPTION

[0025] Referring now to the drawing in which like reference numeralsrefer to like parts throughout, there is seen in FIG. 1 a representationof lungs 10 free from any pulmonary occlusions. In healthy lungs 10,blood flows freely from the pulmonary arteries 12 into the capillaries14 surrounding the individual alveoli 16 of the lungs 10. When inhaledair 18 is drawn into the lungs 10 and alveoli 16, oxygen is transferredfrom the inhaled air 18 to the blood stream and carbon dioxide istransferred out. Inhaled air 18 typically contains an oxygen partialpressure of approximately one hundred (100) torr and a carbon dioxidepartial pressure of zero (0) torr.

[0026] Once the inhaled air 18 reaches the alveoli 16, the oxygencontent decreases while the carbon dioxide content increases until anequilibrium with blood gas levels in the pulmonary arteries 12 isreached. The inhaled air 18 is then, as seen in FIG. 2, expired asexhaled air 20. Exhaled air 20 from properly functioning lungs typicallycontains a partial pressure of oxygen of about eighty (80) torr and apartial pressure of carbon dioxide of about forty (40) torr.

[0027]FIG. 3 depicts the functioning of a respiratory system afflictedwith a pulmonary embolism 22 which, as an example, occludes blood flowto an afflicted lung 24. As a result, there is a reduction in the numberof alveoli 16 that participate in gas exchange. This volume of spaceavailable in the alveoli 16 that is lost from participation is commonlyreferred to as alveolar deadspace. Due to the deadspace and loss oftotal alveolar volume available for gas exchange, afflicted lung 24 doesnot exchange gases as readily as the healthy lung 10. Accordingly,exhaled air 26 contains a higher partial pressure of oxygen and lowerpartial pressure of carbon dioxide than air exhaled from a healthy lung.In the example depicted in FIG. 3, exhaled air 26 exiting therespiratory system contains a partial pressure of oxygen of abouteighty-five (85) torr and a partial pressure of carbon dioxide of abouttwenty (20) torr. Thus, the ratio of carbon dioxide to oxygen in exhaledair 26 from afflicted lung 24 (i.e., 20:85) is smaller than the ratio inexhaled air 20 from healthy lung 10 (i.e., 40:80) as seen in FIG. 2.

[0028] As seen in FIG. 4, a system 28 for measuring and diagnosingpulmonary disorders comprises a measuring unit 30 in combination with adata processing unit 50 and a display screen 60. Measuring unit 30determines the overall flow of air inhaled into and exhaled out of thelungs while simultaneously determining the partial pressure of oxygenand carbon dioxide. Data processing unit 50 computes the concentrationsof carbon dioxide, oxygen, and nitrogen from the partial pressures anddetermines the ratio of carbon dioxide to oxygen from the raw dataobtained by measuring unit 30. The ratio of carbon dioxide to oxygen isthen plotted against expired volume on display screen 60. By comparingthe carbon dioxide ratios to average readings, the likelihood that agiven patient has a pulmonary embolism can be determined.

[0029] Measuring unit 30 comprises a patient mouthpiece 32 connected influid communication to a breathing tube 34 having an open end 42 throughwhich air can be inhaled or exhaled. Measuring unit 30 further comprisesthree sensors; a pneumotach 36, a capnometer 38, and an oxygen monitor40. The three sensors are situated in series and in-line with breathingtube 34 for simultaneously measuring the flow, carbon dioxide, andoxygen levels of inhaled and exhaled air. Infrared and paramagnetic typesensors are preferred respectively. Sensors using spectrometrictechniques may also work for both oxygen and carbon dioxide measurementsproviding they can supply data with rapid enough response time forbreath-to-breath, real-time plotting. The mainstream technique formeasuring the inhaled or exhaled air is preferred, but the sidestreamtechnique may also be effective.

[0030] As seen in FIG. 5, a T-piece adaptor 70 may optionally beprovided at open end 42 of breathing tube 34 for use with patients thatare oxygen dependant. T-piece adapter 70 contains an inlet valve 72 andan outlet valve 74 which properly direct the passage of inhaled andexhaled air through the breathing tube 34. By connecting an oxygendependant patient's supply to the intake valve 72, inhaled air can firstbe passed through the three sensors 36, 38, 40 to establish baselinereadings of the oxygen and carbon dioxide concentrations for comparisonto exhaled air, since an oxygen dependent patient receives air that hasdifferent concentrations than present in ambient air.

[0031] Data processing unit 50 comprises a commercially availablecomputer processor programmed with software for the interpretation ofthe data obtained from measuring unit 30 and background comparison data.Software can be specifically developed to perform the necessarycalculations to determine the partial pressures and carbon dioxide tooxygen ratios or software can optionally be purchased commercially and,if necessary, modified to run the appropriate algorithms. Afteradditional research, the background comparison data can be updated basedon data obtained from use of the invention to further refine expectednormal values.

[0032] Display screen 60 comprises a cathode ray tube or other visualdisplay for displaying computerized data. Screen 60 can optionallydisplay graphs representing predetermined reference or background datafor test populations against which the current readings can be plottedfor a visual comparison. In addition to displaying the carbon dioxide tooxygen ratios as a function of time calculated by data processing unit50, screen 60 may optionally display a plot of the expired oxygen andcarbon dioxide partial pressures. Using this display, a physician mayestimate the efficiency of alveolar ventilation in patients with acuterespiratory distress syndromes to assist in deciding the mechanicalventilation settings.

[0033] In addition to the three primary sensors 36, 38, 40, dataprocessing unit 50 may optionally be connected to a pulse oximeter 44that measures arterial oxygen saturation of hemoglobin in the arterialblood. From this data, and the additional measurement of pH andhemoglobin concentration in a peripheral venous blood sample, thecardiac output of the patient can be calculated according to the Fickequation. In order to perform the Fick equation, the average totaloxygen consumed, the arterial oxygen content and venous oxygen contentmust be determined. The average total oxygen consumed can be determinedfrom the oxygen tension and flow curves over a predetermined timeperiod. For the purposes of determining cardiac output, a one minutetime period is sufficient. The arterial oxygen content can be estimatedby multiplying the arterial oxygen saturation (measured by pulseoximeter 44) by the hemoglobin concentration (determined from the venousblood sample). The venous oxygen content can be calculated bydetermining the nadir (mean lowest) oxygen tension measured duringexpiration over the predetermined time period. From the nadir oxygentension, venous oxygen saturation can be estimated according topublished oxygen binding curves for the measured pH. The venous oxygencontent is then calculated by multiplying the venous oxygen saturationby the venous hemoglobin (measured from the venous blood sample). Oncethese calculations have been made, the cardiac output is determined bydividing the total oxygen consumed by the difference between thearterial oxygen content and the venous oxygen content. The algorithm forthe Fick calculation can be programmed into the data processing unitsoftware and the results displayed on screen 60. The cardiac outputmeasurement is useful for assisting the physician in determining thesuccess or failure of treatment designed to relieve pulmonary vascularobstructions, or to treat circulatory shock.

[0034] Device 28 is used by having a patient breathe (inhale and exhalea predetermined number of times in succession) through mouthpiece 32 ofthe measuring unit 30. As the patient inhales and exhales the pneumotachflow sensor 36, capnometer 38, and oxygen monitor 40 perform theirrespective readings, which are then electrically transmitted via wiresor cabling to data processing unit 50. The programmable software loadedinto data processing unit 50 convert the measurements into volume andconcentration readings, calculate the carbon dioxide to oxygen ratio,and display this ratio on screen 60 in the form of a graph against thevolume of air expired. Readings may be optimized by requiring thepatient to hold in inhaled air for several heartbeats before exhalingthrough the mouthpiece 32 of the measuring unit 30. It is generallyaccepted that patients without a pulmonary embolism will normally have acarbon dioxide to oxygen ratio of 0.30 or greater while patients with apulmonary embolism will have a carbon dioxide to oxygen ratio of 0.25 orless.

[0035] Device 28 may also be used for the detection of whole-body oxygenconsumption and determination of the adequacy of oxygen delivery duringresuscitation from shock. During conditions of systemic inflammation thebody will extract oxygen at higher levels than normal, resulting in anincrease in the carbon dioxide to oxygen ratio in exhaled air. By usingT-piece 70 in the manner explained above, the concentration of theoxygen provided to the patient and the concentration of the oxygenexhaled can be determined. As illustrated in FIG. 6, when the level ofoxygen delivery (i.e., the amount provided minus the amount exhaled)observed at two inspired oxygen concentrations reaches normal levels aphysician has visual conformation that the resuscitation performed isadequate. One method of determining the adequacy of resuscitation is todetermine oxygen delivery at both relatively low fixed concentrations ofoxygen and at relatively high fixed concentration. Relatively lowconcentrations include from about twenty-one to thirty percent (21-30%)oxygen and relatively high oxygen concentrations involve aboutforty-five to fifty percent (45-50%) oxygen. The difference betweenoxygen delivery at relatively low concentrations verses relatively highconcentrations can be compared against a nomogram for healthy patientsof similar age, body mass, body mass index, and gender and used toassess the adequacy of fluid and vasopressor resuscitation.

[0036] Data processing unit 50 can additionally be programmed to displayon screen 60 any of the individual measurements taken by sensors 36, 38,40, and 44, or combinations thereof for diagnostic purposes. Forexample, a plot of the expired carbon dioxide and oxygen concentrationover time could be used to estimate the efficiency of alveolarventilation in patients with acute respiratory distress syndrome.Additionally, the plotted data from sensors 36, 38, 40, and 44 could beused to assist in deciding how to properly adjust mechanical ventilatorssetting, such as the degree of positive end-expiratory pressure, minuteventilation, and peak inspiratory pressure settings, to optimize patientcare. For example, data from sensors 36, 37, 40, and 44, can be plottedindividually in patients who are being mechanically ventilated. Bysimultaneously plotting the partial pressures of oxygen and carbondioxide as a function of volume of each breath, the amount of carbondioxide released and percentage of oxygen extracted can be determined.If the barometric pressure is known or inputted into data processingunit 50, the efficiency of alveolar ventilation during each tidal volumebreath can be calculated. This information can then be used to adjustmechanical ventilation to optimize alveolar efficiency or breathingalveolar ventilation efficiency.

What is claimed is:
 1. A device for non-invasively diagnosing abnormalrespiratory function, comprising: a patient breathing tube; a flow meterconnected to said tube; an oxygen meter connecter to said tube; and acarbon dioxide meter connected to said tube.
 2. The device of claim 1,further comprising an adapter in fluid communication with said tube,wherein said adapter comprises a hollow body having an inlet valvecapable of being connected to patient oxygen source and an outlet valvefor venting expired air.
 3. The device of claim 1, wherein said tubecomprises a mouthpiece in fluid communication with a main body, an inletvalve in fluid communication with said body and adapted for connectionto a patient oxygen source and an outlet valve in fluid communicationwith said body for venting expired air.
 4. A system for non-invasivelydiagnosing abnormal respiratory function, comprising: a patientbreathing tube; a flow meter connected to said tube; an oxygen meterconnecter to said tube; a carbon dioxide meter connected to said tube;and a data processing unit connected to said flow meter, said oxygenmeter, and said carbon dioxide meter.
 5. The system of claim 4, furthercomprising a display screen coupled to said data processing unit.
 6. Thesystem of claim 4, further comprising an arterial pulse oximeterconnected to said data processing unit.
 7. The device of claim 4,further comprising an adapter in fluid communication with said tube,wherein said adapter comprises a hollow body having an inlet valvecapable of being connected to patient oxygen source and an outlet valvefor venting expired air.
 8. The device of claim 4, wherein said tubecomprises a mouthpiece in fluid communication with a main body, an inletvalve in fluid communication with said body and adapted for connectionto a patient oxygen source and an outlet valve in fluid communicationwith said body for venting expired air.
 9. A device for non-invasivelydiagnosing abnormal respiratory function, comprising: means formeasuring the concentration of oxygen and carbon dioxide in air inhaledand exhaled by a subject; means for calculating carbon dioxide to oxygenratios connected to said measuring means; and means for plotting saidratios connected to said calculating means.
 10. A method for diagnosingabnormal respiratory function, comprising the steps of: providing amouthpiece to a patient; allowing said patient to exhale air throughsaid mouthpiece; measuring the oxygen and carbon dioxide partialpressures of the exhaled air; calculating carbon dioxide to oxygenratios for the volume of exhaled air; and determining whether the ratiosindicate abnormal respiratory function.
 11. The method of claim 10,further comprising the steps of: allowing said patient to inhale throughsaid mouthpiece; and measuring the oxygen and carbon dioxide partialpressures of the inhaled air.
 12. The method of claim 10, furthercomprising the step of diagnosing the abnormal respiratory function asproduced by pulmonary embolism if the carbon dioxide to oxygen ratio isless than about 0.25.
 13. The method of claim 10, wherein saiddetermining whether the ratios indicate abnormal function comprisescomparing the ratios to predetermined data from normal populations andpopulations with other causes of abnormal respiratory function whichsimulate pulmonary embolisms.
 14. A method for measuring the response toresuscitation, comprising the steps of: allowing said patient to inhalethrough a mouthpiece; measuring the oxygen and carbon dioxide partialpressures of the inhaled air. allowing said patient to exhale airthrough said mouthpiece; measuring the oxygen and carbon dioxide partialpressures of the exhaled air; calculating the amount of oxygen deliveredto the patient; and determining whether resuscitation is complete. 15.The method of claim 14, wherein the step of determining whetherresuscitation is complete comprises comparing the amount of oxygendelivered to predetermined data from normal populations.
 16. A methodfor measuring a patient's response to resuscitation, comprising thesteps of: providing a device capable of measuring oxygen and carbondioxide partial pressures; supplying a relatively low concentration ofinspired oxygen of about 21 to 30 percent; providing a relatively highconcentration of inspired oxygen of about 45 to 50 percent; calculatingthe amount of oxygen delivered to the patient for both the lowerconcentration of inspired oxygen and the higher concentration ofinspired oxygen; and comparing the difference in oxygen deliveredbetween the lower concentration and the higher concentration withexpected values.
 17. A method of measuring the efficiency of alveolarventilation, comprising the steps of: providing a mouthpiece to apatient; allowing said patient to inhale through said mouthpiece;measuring the oxygen and carbon dioxide partial pressures of the inhaledair; calculating the amount of oxygen delivered; calculating the amountof carbon dioxide released; determining the efficiency of alveolarventilation during each tidal volume breath.
 18. A method of measuringthe cardiac output of a patient, comprising the steps of: providing amouthpiece to a patient; allowing said patient to inhale and exhalethrough said mouthpiece; continuously measuring oxygen partial pressuresof the inhaled and exhaled air; continuously measuring the arterialoxygen saturation through pulse oximetry; measuring the pH andhemoglobin concentration of a venous blood sample; and calculating thecardiac output.
 19. The method of claim 18, wherein the step ofcalculating the cardiac output further comprises the steps of:calculating the average total oxygen consumed over a predetermined timeperiod; calculating the arterial oxygen content as the product ofmeasured arterial oxygen saturation and hemoglobin concentration;determining the lowest mean oxygen tension during expiration over thepredetermined time period; estimating the venous oxygen saturation fromthe mean lowest oxygen tension according to published oxygen bindingcurves for the measured pH; calculating the venous oxygen content as theproduct of venous oxygen saturation and the measured hemoglobinconcentration; and dividing the average total oxygen consumed by thedifference between the arterial oxygen content and venous oxygencontent.